drugs are now available for the treatment of acromegaly. Medical therapy is .... The independent clinical risk factors in these guidelines include parental history.
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Clinical Medicine 2013, Vol 13, No 2: 170–5
DRUG THERAPIES IN...
Recent advancements in the drug treatment of endocrine diseases Amir H Sam and Karim Meeran ABSTRACT – Recent years have seen several advances in the management of endocrine diseases. These include novel drugs developed as a consequence of better understanding of the pathophysiology of endocrine conditions, as well as improved delivery methods for existing drugs. In this article, we summarise recent studies evaluating several drugs used in the treatment of endocrine disorders. KEY WORDS: endocrine diseases, pharmacotherapy
Introduction Control of hormone hypersecretion and replacement of hormone deficiencies are the mainstay of treatment in endocrinology. The ultimate goal of treatment is to reduce the longterm morbidity and mortality associated with hormone hypoor hypersecretion and to improve the quality of life. Here, we review the evidence for the efficacy and safety of some of the recent drugs used in the pharmacotherapy of several endocrine diseases.
Cushing’s disease The primary treatment for Cushing’s disease is surgical removal of the adrenocorticotropic hormone (ACTH)-secreting pituitary tumour. Medical control of hypercortisolism is required when surgery is contraindicated, in preparation for surgery and in cases of persistence or recurrence of hypercortisolism following surgery. Medication commonly used includes ketoconazole and metyrapone. Ketoconazole blocks the first step (sidechain cleavage) and, to a lesser extent, the last step in cortisol biosynthesis (ie conversion of 11-deoxycortisol to cortisol) by inhibiting 11 beta-hydroxylase. Metyrapone inhibits the last step in cortisol biosynthesis. Two medical treatments targeting the pituitary corticotroph adenoma have recently shown potential benefit in the treatment of Cushing’s disease.
Cabergoline Dopamine (D)2 receptors have been identified in corticotroph tumours. Treatment with cabergoline (a D2 agonist) is associated with a reduction in 24-h urinary free cortisol (UFC) in patients with Cushing’s disease.1,2 In one study, cabergoline normalised 24-h UFC after six months in 25% of patients with Cushing’s disease unsuccessfully treated by surgery at doses ranging from Amir H Sam, clinical lecturer; Karim Meeran, professor of endocrinology Imperial Centre for Endocrinology, Imperial College London
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2 to 3 mg/week.1 In another study, normalisation of UFC was achieved in approximately 37% of patients with Cushing’s disease within 3–6 months. In this study, 30% of patients had sustained normalisation of UFC after a mean of 37 months, with a mean dose of 2.1 mg/week of cabergoline.2 Close follow-up is necessary for dose adjustments. However, UFC is not a good marker of cortisol dynamics and normalisation of UFC does not mean that the patient is necessarily in remission. Plasma cortisol concentrations more accurately reflect cortisol exposure and cortisol day curves showing a normal diurnal rhythm would give a better indication of disease response to cabergoline.
Pasireotide Pasireotide is a somatostatin analogue that binds to four of the five somatostatin receptors (1, 2, 3 and 5) and has highest affinity for subtype 5. In a recent randomised double-blind trial, patients with either newly diagnosed Cushing’s disease who were not eligible for surgery or those with persistent and/or recurrent Cushing’s disease after surgery received pasireotide subcutaneously at 2 doses, 600 µg or 900 µg, twice daily.3 Approximately 26% of patients receiving the higher dose in the study achieved normalisation of UFC level at 6 months without dose uptitration. Serum and salivary cortisol and plasma ACTH levels decreased in both dose groups, and clinical signs and symptoms of Cushing’s disease improved.3 Pasireotide was associated with hyperglycaemia-related adverse events in approximately 73% of patients. Treatment with a glucose-lowering medication was started in 46% of patients.3 In a report of 17 patients with Cushing’s disease, a combination of cabergoline and pasireotide normalised UFC in four out of 12 patients (33%) not responding to pasireotide monotherapy.4 Therefore, these drugs might offer some improvement in cortisol levels when other treatments have failed, but they should not be used as first-line therapy.
Acromegaly The first-line treatment of patients with acromegaly is surgery. Trans-sphenoidal surgery by a dedicated experienced pituitary surgeon should be offered to all patients with a microadenoma or a macroadenoma that appears to be fully resectable, or is causing visual impairment. Remission rates for acromegaly surgery improve with establishment of a specialist surgical service, with a reduction in surgeon numbers.5 Primary medical treatment can be offered to patients who are unfit for surgery, refuse surgery or who are not amenable to surgical cure.6,7 Several drugs are now available for the treatment of acromegaly. Medical therapy is often used when surgery alone has not been successful in achieving disease control. The updated consensus guidelines
© Royal College of Physicians, 2013. All rights reserved.
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Recent advancements in the drug treatment of endocrine diseases
of 2010 define disease control as a growth hormone (GH) nadir of
